Sex-specific Association of Subclinical Hypothyroidism With Incident Metabolic Syndrome: A Population-based Cohort Study

Objective: Subclinical hypothyroidism is known to increase the risk of cardiovascular diseases and mortality. However, the longitudinal association between subclinical hypothyroidism and incident metabolic syndrome remains unclear. Methods: A total of 3615 participants from Beijing Health Management Cohort were enrolled from 2012 to 2014 and followed through 2019. People were placed into subclinical hypothyroidism and euthyroidism groups according to serum-free thyroxine and TSH concentrations. We used Cox proportional hazards regression models to investigate the relationship between TSH level and incident metabolic syndrome considering the modification effect of sex and age. Results: Of 3615 participants, 1929 were men (53.4%); mean (SD) age was 43.51 (11.73) years. Throughout the follow-up (median [interquartile range], 3.0 [2.8-3.2] years), 738 individuals developed metabolic syndrome. Subclinical hypothyroidism was significantly associated with metabolic syndrome development only in men, and the adjusted hazard ratio was 1.87 (95% CI, 1.21-2.90) compared with euthyroidism group. Of note, there was no increased risk of metabolic syndrome in people aged 50 years or older with subclinical hypothyroidism. Conclusions: Subclinical hypothyroidism is associated with incident metabolic syndrome in young men. Further studies are needed to evaluate the targeted threshold and benefit of thyroid hormone replacement therapy for metabolic health.